The two dopamine receptor hypothesis (which was formulated in ETB) provided a rational basis for studying the biochemical and physiological effects of dopamine. This project investigates the pharmacology and biochemistry of the D-1 and D-2 dopamine receptors. The knowledge gained about these receptors may facilitate the development of drugs effective in the treatment of Parkinson's disease, endocrine and psychiatric disorders; hypertension and antiemetics. The pharmacology of the D-1 and D-2 dopamine receptors was investigated in experiments using apomorphines, tetralins and benzazepines. Aporphines with R and S configurations at position 6a have divergent pharmacologies: the S-aporphines are dopamine receptor antagonists while certain R-aporphines are dopamine receptor agonists. Because the aporphines have relatively rigid structures in which a limited number of conformations are possible, it was productive to compare their structures with those of other, more flexible molecules to gain insight into how drugs stimulate or block dopamine receptors. Certain tetralins were potent, selective D-2 agonists; these molecules permitted differences between the pharmacological properties of the D-1 and D-2 dopamine receptors to be identified. Certain benzazepines are selective towards the D-1 receptor; from an understanding of the structure-activity relationship between these molecules, it was possible to begin the development of new research tools for the D-1 receptor. The cell biology of the pituitary gland and the presence of cAMP-dependent protein kinase in normal and malignant pituitary tissue was investigated. The tumors were especially convenient because they provide much more tissue than is routinely available from the intermediate lobe. The data obtained supports the view that cAMP modulates calcium-dependent hormone release. The ability of the D-2 receptor to regulate the synthesis of proopiomelanocortin and the melanotrophic peptides derived from this large prohormone was investigated. A series of in vitro experiments using drugs discriminating between the D-1 and D-2 receptor could markedly inhibit the synthesis of the melanotrophic peptides.